1. Field of the Invention
The present invention relates generally to a non-toxic lipid conjugated with a cationic amino acid containing a guanidino group. Specifically, the naturally-occuring lipid dioleoylphosphatidylethanolamine (DOPE) is combined with the naturally-occurring amino acid Arginine. These compounds are useful for encapsulating and delivering pharmaceuticals and poly and oligonucleotides. These compounds improve over current compounds, because they are composed of non-toxic and, in the case of Arginine conjugated with DOPE (Arg-PE), natural components, and therefore result in minimal unwanted side effects. Methods of use of the cationic lipids are also claimed.
2. Background of the Invention
Cationic lipids have been described in the past. Most of the cationic lipids previously described involve synthetic (non-naturally-occurring) components. The three patents provided in this background to the invention also describe many non-naturally-occurring components.
Stadler, et. al., U.S. Pat. No. 5,286,634 describes a process for transferring nucleic acids into cells, most particularly plant cells, using a polycationic compound in conjunction with a cationic lipid.
Felgner, et. al., U.S. Pat. No. 5,264,618 describes several cationic lipids, but is limited to those with an ammonium group. The present cationic lipid does not utilize an ammonium group.
Feigner, et al., U.S. Pat. No. 5,459,127 is a continuation of the above patent, and claims the formulations and methods of the patent above.
Gershon, et al., 32 Biochemistry 7143 (1993). This journal article describes a theory of a mechanism of action for the transfer of nucleic acids via cationic liposomes. Although it discusses PE (a naturally-occurring lipid), it does not describe it in conjunction with arginine.
Behr, 5 Bioconjugate Chem. 382 (1994) is a review article which describes many cationic lipids, but not a Arg-PE construct.
Remy et al., 5 Bioconjugate Chem. 647 (1995) is an article following-up the article above, in the same journal. It describes DOPE conjugated with spermine. It does not disclose an Arg-PE construct.
Chang & Brenner, citation unknown, describes protocols for transferring cationic liposomes into cells. It does not disclose the Arg-PE construct.